Endocrine Abstracts

Background: Pituitary adenomas (PA) and pheochromocytomas/paraganglioma (pheo/PGL) can occur in the same patient due to coincidence or of shared pathogenesis. There is evidence that, at least in some cases, classical pheo/PGL predisposing genes, may also play a role in pituitary tumorigenesis. A new condition called ‘the three P Association’ (3PAs) for the combination of PA with pheo/PGL has been recently described in patients with or without succinate dehydrogenase (SDHx) germline mutations.

Aim: To report our experience on 3PAs in three patients. Case 1: A 54-year-old male patient with bilateral pheochromocytoma underwent bilateral adrenalectomy. Three years later he was diagnosed with growth hormone-secreting pituitary adenoma that was completely resected after transsphenoidal surgery. Genetic screening for pheo/PGL genes (RET, VHL, SDHB and SDHD) were negative (including sequencing and gross delection analysis). Case 2: A 38-year-old-female patient was initially seen for macroprolactinoma and chronically treated with dopamine agonist. Four years later the patient was diagnosed with multiple PGL (cervical and unresectable mediastinal PGL), currently under somatostatin analogue therapy. Her brother was operated for PGL and gene study revealed a SDHB exon 1 deletion (genetic disorder associated with familial PGL type 4). This genetic rearrangement was also detected in her mother and sister. Case 3: A 55-year-old female patient was diagnosed with a right pheochromocytoma. She underwent right adrenalectomy. Five years later she was diagnosed with GH-secreting pituitary microadenoma and treated with transsphenoidal surgery. She was also diagnosed with primary hyperparathyroidism without surgical criteria. Genetic study for MEN 1, RET and VHL was negative.

Conclusion: The association of PA and pheo/PGL is an exceptional event, but recent insights provide strong evidence that PA can develop in patients with pheo/PGL or germline SDHx subunit mutations. Genetic testing should be considered in all patients or families with 3PAs.